Hypoxia, not hypercapnia, induces cardiorespiratory failure in rats.

Mechanical respiratory loads induce cardiorespiratory failure, presumably by increasing O2 demand concurrently with decreases in O2 availability (decreased PaO2). We tested the hypothesis that asphyxia alone can cause cardiorespiratory failure ("failure") in pentobarbital-anesthetized rats. We also tested the hypothesis that hypoxia, not hypercapnia, is responsible by supplying supplemental O2 during mechanical loading in a separate group of rats. Asphyxia (mean PaO2 and PaCO2 of 43 and 69mmHg, respectively) resulted in failure, evident as a slowing of mean respiratory frequency (133-83breaths/min) and a sudden and large drop in mean arterial pressure (71-47mmHg), after 214±66min (n=16; range 117-355min). Neither respiratory drive nor heart rate decreased, indicating that failure was peripheral, not central. Of 8 rats tested after 3h of asphyxia for the presence in blood of cardiac troponin T, all were positive. In an additional 6 rats, normocapnic hypoxia (mean PaCO2 and PaO2 were 39±2.2 and 41±3.1mmHg, respectively) caused failure after an average 205min (range 181-275min), no different from that of asphyxic rats. In the 6 rats that breathed O2 during an initially moderate inspiratory resistive load, endurances exceeded 7h (failure occurring only because we increased the load after 6h) and tracheal pressure and left ventricular dP/dt were maintained despite supercarbia (PaCO2>150mmHg). Thus, asphyxia alone can induce failure, the failure is due to hypoxia, not hypercapnia, and hypercapnia has minimal effects on cardiac and respiratory muscle function in the presence of hyperoxia.

CO(2) rebreathing: an undergraduate laboratory to study the chemical control of breathing.

The Read CO2 rebreathing method (Read DJ. A clinical method for assessing the ventilatory response to carbon dioxide. Australas Ann Med 16: 20-32, 1967) provides a simple and reproducible approach for studying the chemical control of breathing. It has been widely used since the modifications made by Duffin and coworkers. Our use of a rebreathing laboratory to challenge undergraduate science students to investigate the control of breathing provided 8 yr of student-generated data for comparison with the literature. Students (age: 19-22 yr, Research Ethics Board approval) rebreathed from a bag containing 5% CO2 and 95% O2 (to suppress the peripheral chemoreflex to hypoxia). Rebreathing was performed, and ventilation measured, after hyperventilation to deplete tissue CO2 stores and enable the detection of the central chemoreflex threshold. We analyzed 43 data sets, of which 10 were rejected for technical reasons. The mean threshold and ventilatory sensitivity to CO2 were 43.3 ± 3.8 mmHg and 4.60 ± 3.04 l·min(-1)·mmHg(-1) (means ± SD), respectively. Threshold values were normally distributed, whereas sensitivity was skewed to the left. Both mean values agreed well with those in the literature. We conclude that the modified rebreathing protocol is a robust method for undergraduate investigation of the chemical control of breathing.

Hypercapnia and surgical site infection: a randomized trial.

BACKGROUND: Tissue oxygenation is a strong predictor of surgical site infection (SSI). Mild intraoperative hypercapnia increases peripheral, gastrointestinal, and splanchnic tissue oxygenation and perfusion. Hypercapnia also has anti-inflammatory effects. However, it is unknown whether hypercapnia reduces SSI risk. We tested the hypothesis that mild intraoperative hypercapnia reduces the risk of SSI in patients having colon resection surgery. METHODS: With institutional review board approval and subject consent, patients having elective colon resection (e.g. hemicolectomy and low-anterior resection) expected to last >2 h were randomly assigned to intraoperative normocapnia (PE'CO2 ≈ 35 mm Hg; n=623) or hypercapnia ( PE'CO2 ≈ 50 mm Hg; n=592). Investigators blinded to group assignment evaluated perioperative SSI (Center for Disease Control criteria) for 30 postoperative days. SSI rates were compared. RESULTS: Patient and surgical characteristics were comparable among the groups. The SSI rate for normocapnia was 13.3%, and for hypercapnia, it was 11.2% (P=0.29). The Executive Committee stopped the trial after the first a priori determined statistical assessment point because of much smaller actual effect compared with the projected. However, because the actual difference found in the SSI rates (15-16%) were within the 95% confidence intervals (CIs) of the projected relative difference of 33% (95% CI -43 to +24%), our results cannot be considered as 'no difference', and cannot exclude a Type II error. Time to first bowel movement was half-a-day shorter in the hypercapnia group. CONCLUSIONS: Mild hypercapnia appears to have little or-possibly-no ability to prevent SSI after colon resection. Other strategies for reducing SSI risk should thus take priority.

Changes in serum fast and slow skeletal troponin I concentration following maximal eccentric contractions.

OBJECTIVES: We tested the hypothesis that fast skeletal muscle troponin I (fsTnI) concentration in serum would increase more than those of slow skeletal muscle troponin I (ssTnI) after eccentric exercise of the elbow flexors using a sensitive blood marker to track fibre specific muscle damage. DESIGN: Observational comparison of response in a single experimental group. METHODS: Eight young men (26.4±6.2 years) performed 210 (35 sets of 6) eccentric contractions of the elbow flexors on an isokinetic dynamometer with one arm. Changes in serum fsTnI and ssTnI concentrations, serum creatine kinase (CK) activity, and maximal voluntary isometric contraction torque (MVIC) before and 1, 2, 3, 4 and 14 days following exercise were analysed by a Student-Newman-Keuls multiple comparison test. The relationship between serum CK activity and fsTnI or ssTnI concentrations was determined using a Pearson's product moment correlation. RESULTS: Significant (P<0.05) decreases in MVIC and increases in serum CK activity and fsTnI were evident after exercise, but ssTnI did not change. The time course of changes in fsTnI was similar to that of CK, peaking at 4 days post-exercise, and the two were highly correlated (r=0.8). CONCLUSIONS: Increases in serum fsTnI concentrations reflect muscle damage, and it seems likely that only fast twitch fibres were damaged by eccentric contractions.

Repeated inspiratory occlusions in anesthetized rats acutely increase blood coagulability as assessed by thromboelastography.

Many of the components contributing to coagulability are enhanced by repeated episodes of hypoxia, as occurs in obstructive sleep apnea, but no one has yet measured the global hemostatic properties of blood in an animal model of this disease. Using thromboelastography, a hemostatic assay, we measured hemostasis in six pentobarbital-anesthetized rats before and after 3h of repeated inspiratory occlusions lasting 30s applied every 2 min and compared the results to those in six identically prepared rats before and after 3h of resting breathing. Rats subjected to occlusions displayed faster onset of clotting (p<0.031) and more rapid coagulation (p<0.031). Thus, repeated inspiratory occlusions acutely cause hypercoagulability in rats. Thromboelastography, a simple test of hemostasis, may help evaluate the factors responsible for this increase and, in patients with obstructive sleep apnea, the risk of future cardiovascular disease.

Precise control of end-tidal carbon dioxide levels using sequential rebreathing circuits.

Anaesthesiologists have traditionally been consulted to help design breathing circuits to attain and maintain target end-tidal carbon dioxide (P(ET)CO2). The methodology has recently been simplified by breathing circuits that sequentially deliver fresh gas (not containing carbon dioxide (CO2)) and reserve gas (containing CO2). Our aim was to determine the roles of fresh gas flow, reserve gas PCO2 and minute ventilation in the determination of P(ET)CO2. We first used a computer model of a non-rebreathing sequential breathing circuit to determine these relationships. We then tested our model by monitoring P(ET)CO2 in human volunteers who increased their minute ventilation from resting to five times resting levels. The optimal settings to maintain P(ET)CO2 independently of minute ventilation are 1) fresh gas flow equal to minute ventilation minus anatomical deadspace ventilation, and 2) reserve gas PCO2 equal to alveolar PCO2. We provide an equation to assist in identifying gas settings to attain a target PCO2. The ability to precisely attain and maintain a target PCO2 (isocapnia) using a sequential gas delivery circuit has multiple therapeutic and scientific applications.

A simple apparatus for accelerating recovery from inhaled volatile anesthetics.

UNLABELLED: Hyperpnea increases anesthetic elimination but is difficult to implement with current anesthetic circuits without decreasing arterial PCO2. To circumvent this, we modified a standard resuscitation bag to maintain isocapnia during hyperpnea without rebreathing by passively matching inspired PCO2 to minute ventilation. We evaluated the feasibility of using this apparatus to accelerate recovery from anesthesia in a pilot study in four isoflurane-anesthetized dogs. The apparatus was easy to use, and all dogs tolerated being ventilated with it. Under our experimental conditions, isocapnic hyperpnea reduced the time to extubation by 62%, from an average of 17.5 to 6.6 min (P = 0.012), but not time from extubation to standing unaided. This apparatus may provide a practical means of applying isocapnic hyperpnea to shorten recovery time from volatile anesthetics. IMPLICATIONS: A simple modification to a standard resuscitation bag allows one to increase ventilation without decreasing blood carbon dioxide levels. In dogs, we confirmed that this circuit can be used to accelerate the elimination of and recovery from volatile anesthetics.

Tracheal constrictor drive above the apneic threshold in anesthetized dogs.

We have previously shown that raising arterial PCO(2) (Pa(CO(2))) by small increments in dogs ventilated below the apneic threshold (AT) results in almost complete tracheal constriction before the return of phrenic activity (Dickstein JA, Greenberg A, Kruger J, Robicsek A, Silverman J, Sommer L, Sommer D, Volgyesi G, Iscoe S, and Fisher JA. J Appl Physiol 81: 1844-1849, 1996). We hypothesized that, if increasing chemical drive above the AT mediates increasing constrictor drive to tracheal smooth muscle, then pulmonary slowly adapting receptor input should elicit more tracheal dilation below the AT than above. In six methohexital sodium-anesthetized, paralyzed, and ventilated dogs, we measured changes in tracheal diameter in response to step increases in tidal volume (VT) or respiratory frequency (f) below and above the AT at constant Pa(CO(2)) ( approximately 40 and 67 Torr, respectively). Increases in VT (400-1,200 ml) caused significantly more (P = 0.005) tracheal dilation below than above AT (7.0 +/- 2.2 vs. 2.8 +/- 1.0 mm, respectively). In contrast, increases in f (14-22 breaths/min) caused similar (P = 0.93) tracheal dilations below and above (1.0 +/- 1.3 and 1.0 +/- 0.8 mm, respectively) AT. The greater effectiveness of dilator stimuli below compared with above the AT is consistent with the hypothesis that drive to tracheal smooth muscle increases even after attainment of maximal constriction. Our results emphasize the importance of controlling PCO(2) with respect to the AT when tracheal smooth muscle tone is experimentally altered.

Segmental responses of abdominal motoneurons in decerebrate cats.

As a first step towards elucidating the synaptic organization underlying segmental responses of abdominal muscles I recorded the responses of branches of the left cranial (L(1)L) and caudal (L(2)L) and right caudal (L(2)R) lumbar (iliohypogastric) nerves to electrical shocks of different intensities to the caudal branch of L(2)L in nine decerebrate paralyzed and ventilated cats. If such reflex responses subserve a respiratory function, then they should be bilaterally similar; if they do not, lateral asymmetry should be evident. At intensities activating only large diameter axons (i.e. spindle and tendon organ afferents), stimulation typically elicited in the rostral branch of L(2)L a brief (approximately 1.6 ms) short-latency (approximately 1.8 ms) excitation followed by a suppression of activity (approximately 8-26 ms). Responses increased in amplitude as stimulus intensity increased, the suppression of activity being interrupted by an excitation (latency approximately 5. 4 ms, duration approximately 3.6 ms) in four cats. L(1)L responses were similar. Contralateral responses in the same segment (L(2)R) in five cats consisted of a suppression of activity in four, a short-latency (approximately 3.3 ms) excitation being present in three; increases in stimulus intensity in two additional cats elicited these excitatory and inhibitory responses. I conclude: (1) the variable responses between cats reflect differences in nerve bundles and, therefore, target muscles, from which the recordings were made; and (2) because of the lateral asymmetry of responses, abdominal afferent activation elicited postural (rotational) rather than respiratory reflexes.

A simple "new" method to accelerate clearance of carbon monoxide.

The currently recommended prehospital treatment for carbon monoxide (CO) poisoning is administration of 100% O(2). We have shown in dogs that normocapnic hyperpnea with O(2) further accelerates CO elimination. The purpose of this study was to examine the relation between minute ventilation (V E) and the rate of elimination of CO in humans. Seven healthy male volunteers were exposed to CO (400 to 1,000 ppm) in air until their carboxyhemoglobin (COHb) levels reached 10 to 12%. They then breathed either 100% O(2) at resting V E (4.3 to 9.0 L min) for 60 min or O(2) containing 4.5 to 4.8% CO(2) (to maintain normocapnia) at two to six times resting V E for 90 min. The half-time of the decrease in COHb fell from 78 +/- 24 min (mean +/- SD) during resting V E with 100% O(2) to 31 +/- 6 min (p < 0. 001) during normocapnic hyperpnea with O(2). The relation between V E and the half-time of COHb reduction approximated a rectangular hyperbola. Because both the method and circuit are simple, this approach may enhance the first-aid treatment of CO poisoning.

Hypoxemia-induced modification of troponin I and T in canine diaphragm.

Impaired muscle function (fatigue) may result, in part, from modification of contractile proteins due to inadequate O(2) delivery. We hypothesized that severe hypoxemia would modify skeletal troponin I (TnI) and T (TnT), two regulatory contractile proteins, in respiratory muscles. Severe isocapnic hypoxemia (arterial partial pressure of O(2) of approximately 25 Torr) in six pentobarbital sodium-anesthetized spontaneously breathing dogs increased respiratory frequency and electromyographic activity of the diaphragm and internal and external obliques, with death occurring after 131-285 min. Western blot analysis revealed proteolysis of TnI and TnT, 17.5- and 28-kDa fragments, respectively, and higher molecular mass covalent complexes, one of which (42 kDa) contained TnI (or some fragment of it) and probably TnT in the costal and crural diaphragms but not the intercostal or abdominal muscles. These modifications of myofibrillar proteins may provide a molecular basis for contractile dysfunction, including respiratory failure, under conditions of limited O(2) delivery.

Isocapnic hyperpnea accelerates carbon monoxide elimination.

A major impediment to the use of hyperpnea in the treatment of CO poisoning is the development of hypocapnia or discomfort of CO2 inhalation. We examined the effect of nonrebreathing isocapnic hyperpnea on the rate of decrease of carboxyhemoglobin levels (COHb) in five pentobarbital-anesthetized ventilated dogs first exposed to CO and then ventilated with room air at normocapnia (control). They were then ventilated with 100% O2 at control ventilation, and at six times control ventilation without hypocapnia ("isocapnic hyperpnea") for at least 42 min at each ventilator setting. We measured blood gases and COHb. At control ventilation, the half-time for elimination of COHb (t1/2) was 212 +/- 17 min (mean +/- SD) on room air and 42 +/- 3 min on 100% O2. The t1/2 decreased to 18 +/- 2 min (p < 0.0005) during isocapnic hyperpnea. In two similarly prepared dogs treated with hyperbaric O2, the t1/2 were 20 and 28 min. We conclude that isocapnic hyperpnea more than doubles the rate of COHb elimination induced by normal ventilation with 100% O2. Isocapnic hyperpnea could improve the efficacy of the standard treatment of CO poisoning, 100% O2 at atmospheric or increased pressures.

Control of abdominal muscles.

Abdominal muscles serve many roles; in addition to breathing, especially at higher levels of chemical drive or at increased end-expiratory lung volumes, they are responsible for, or contribute to, such protective reflexes as cough, sneeze, and vomiting, generate the high intra-abdominal pressures necessary for defecation and parturition, are active during postural adjustments, and play an essential role in vocalization in many species. Despite this widespread involvement, however, their control has, with rare exceptions, received little attention for two major reasons. First, in most anesthetized or decerebrate preparations, they are relatively inactive at rest, in part because the position of the preparation (supine or prone with abdomen supported), reduces lung volume and, therefore, their activity. Second, unlike phrenic motoneurons innervating the diaphragm, identification of motoneurons to a particular abdominal muscle is difficult. At the lumbar level, a given motoneuron may innervate any one of the four abdominal muscles; at the thoracic level, they are also intermixed with those innervating the intercostals. The two internal muscles, the internal oblique and the transverse abdominis, respond more to increases in chemical or volume-related drive than the two external muscles, the rectus abdominis and external oblique; the basis for this differential sensitivity is unknown. Segmental reflexes at the thoracic and lumbar levels are sufficient to activate abdominal motoneurons in the absence of descending drive but the basis for these reflex effects is also unknown. Neuroanatomical experiments demonstrate many more inputs to, and outputs from, the nucleus retroambigualis, the brainstem region in which the premotor neurons are located, than can be accounted for by their respiratory role alone. These other connections likely subserve activities other than respiration. Studies of the multifunctional roles of the abdominal muscles, on the basis of recent work, hold considerable promise for improving our understanding of their control.

Chemoreflex thresholds to CO2 in decerebrate cats.

We used a modified rebreathing technique to measure chemoreflex thresholds to CO2 in decerebrate, paralyzed and ventilated cats. Cats were hyperventilated to neural apnea (PaCO2 < 15 mmHg) with one ventilator and then switched to a rebreathing circuit consisting of a balloon inside a bottle connected to a second ventilator. The volume of the circuit was approximately 110 ml. The balloon contained 5% CO2:95% O2 for hyperoxic rebreathing or approximately 5% CO2 with 11 or 6.5% O2 for moderately and severely hypoxic rebreathing. A plateau in CO2 concentration at the onset of rebreathing indicated equilibration of CO2 between the circuit, alveolar gas and venous and arterial blood. After rapid equilibration of CO2 between the cat and the circuit, CO2 increased linearly with time during rebreathing. Under hyperoxic conditions, phrenic activity began to increase at an end-tidal P(CO2) (PET(CO2)) of 35.1 +/- 6.1 (SD) mmHg (n = 8); during hypoxia, phrenic activity began to increase at a significantly lower PET(CO2) of 27.8 +/- 4.8 mmHg (P < 0.01, n = 6). We interpret these values as the central and peripheral chemoreflex thresholds to CO2, respectively. Persistent phrenic activity prevented determination of a threshold during severe hypoxic rebreathing. Our modified method of hyperoxic and hypoxic rebreathing allows detection of the effects of hypoxia on the central and peripheral chemoreflex thresholds and, within a cat, measurements of chemoreflex sensitivities.

A simple breathing circuit minimizing changes in alveolar ventilation during hyperpnoea.

Many clinical and research situations require maintenance of isocapnia, which occurs when alveolar ventilation (V'A) is matched to CO2 production. A simple, passive circuit that minimizes changes in V'A during hyperpnoea was devised. It is comprised of a manifold, with two gas inlets, attached to the intake port of a nonrebreathing circuit or ventilator. The first inlet receives a flow of fresh gas (CO2=0%) equal to the subject's minute ventilation (V'E). During hyperpnoea, the balance of V'E is drawn (inlet 2) from a reservoir containing gas, the carbon dioxide tension (PCO2) approximates that of mixed venous blood and therefore contributes minimally to V'A. Nine normal subjects breathed through the circuit for 4 min at 15-31 times resting levels. End-tidal PCO2 (Pet,CO2) at rest, 0, 1.5 and 3.0 min were (mean+/-SE) 5.1+/-0.1 kPa (38.1+/-1.1 mmHg), 4.9+/-0.1 kPa (36.4+/-1.1 mmHg), 5.0+/-0.2 kPa (37.8+/-1.6 mmHg) and 5.0+/-0.2 kPa (37.6+/-1.4 mmHg) (p=0.53, analysis of variance (ANOVA)), respectively; without the circuit, Pet,CO2 would be expected to have decreased by at least 2.7 kPa (20 mmHg). Six anaesthetized, intubated dogs were first ventilated at control levels and then hyperventilated by stepwise increases in either respiratory frequency (fR) from 10 to 24 min(-1) or tidal volume (VT) from 400 to 1,200 mL. Increases in fR did not significantly affect arterial CO2 tension (Pa,CO2) (p=0.28, ANOVA). Only the highest VT decreased Pa,CO2 from control (-0.5 +/- 0.3 kPa (-3.4 +/- 2.3 mmHg), p<0.05). In conclusion, this circuit effectively minimizes changes in alveolar ventilation and therefore arterial carbon dioxide tension during hyperpnoea.

Effects of stimulation of phrenic afferents on cervical respiratory interneurones and phrenic motoneurones in cats.

1. In ten decerebrate, paralysed and ventilated cats, we tested the hypothesis that cervical (C5) respiratory interneurones mediate inhibition of phrenic motoneurone activity resulting from single shocks to the phrenic nerve. 2. Stimulus intensities sufficient to activate all afferents elicited (latency, 4.0 +/- 0.9 ms, mean +/- S.D.) a graded suppression of ipsilateral, but not contralateral (five of seven cats) phrenic nerve activity lasting, in six of seven cats, more than 70 ms and interrupted by a brief (approximately 6-18 ms duration) excitation at latencies between 7 and 30 ms. 3. In twenty-five ipsilateral motoneurones, peristimulus time average of the membrane potentials (-61 +/- 10 mV) showed no effect in eleven; of the fourteen that responded, ten had initial EPSPs (latency, 17.6 +/- 3.0 ms) and four initial IPSPs (latencies, 2.25-4.3 ms). Only one motoneurone had both. No responses with latencies > 60 ms were observed. 4. Peristimulus time averages of extracellular activity of thirty ipsilateral interneurones, twenty-five firing in inspiration (I) and five in expiration (E), showed diverse responses. The initial response of I interneurones was an excitation in eleven, a suppression of activity in nine, and no response in five. Latencies of excitations ranged from 2 to 36.5 ms (median, 14 ms) with durations ranging from 2 to 7 ms (mean, 4.4 +/- 1.6 ms). Latencies of suppression of activity ranged from 2 to 29 ms (median, 10 ms). Two E interneurones were excited (latencies, 11 and 15 ms; durations, 3.5 and 2 ms), two inhibited (latencies, 2 and 12 ms; durations, > 40 and 17 ms, respectively), and one did not respond. 5. In nine interneurones (seven I, two E), peristimulus time averages of the membrane potentials (mean, -62 +/- 14 mV) revealed no effect on three (all I). Of the six that responded, four (three I) had initial IPSPs, two (one I, one E) initial EPSPs. EPSPs had latencies of 11.5 (I interneurone) and 22 ms (E interneurone); the latencies of the IPSPs were 2.75, 3.20, and 2.3 ms for the I interneurones and 15.9 ms for the E interneurone). No responses with latencies > 30 ms were observed. 6. The diverse responses of cervical respiratory interneurones indicates that they do not mediate the prolonged suppression of ipsilateral phrenic activity elicited by stimulation of phrenic afferents. The suppression may result from activation of normally quiescent inhibitory interneurones or from presynaptic inhibition.

The possible role of C5 segment inspiratory interneurons investigated by cross-correlation with phrenic motoneurons in decerebrate cats.

We tested the role of C5 segment inspiratory interneurons in transcribing central respiratory drive to phrenic motoneurons and mediating intersegmental reflexes by cross-correlating the spontaneous activity of 26 interneurons with that of the ipsi -and contralateral C5 phrenic nerves in decerebrate cats. There were 10 interneurons that discharged only during inspiration (phrenic burst) and 16 that discharged tonically with increased firing during inspiration. Of the cross-correlograms for 26 of the interneurons with the ipsilateral phrenic, 20 were flat and 2 had peaks centred about time zero, interpreted as a common activation of the interneurons and motoneurons. The cross-correlograms for 4 other interneurons had troughs centred about time zero, interpreted as a synchronous excitation of the interneurons and inhibition of the motoneurons. Of the cross-correlograms for 23 interneurons with the contralateral phrenic, 22 were flat and 1 had a peak centred about time zero, interpreted as a common activation of the interneuron and motoneurons. Nine of ten cross-correlograms between pairs of interneurons were flat; one had a peak centred about time zero. We conclude that, despite their inspiratory modulated discharge patterns, there is no evidence from this study that the C5 segment inspiratory interneurons convey central respiratory drive to C5 phrenic motoneurons.

Phrenic motoneuron discharge during sustained inspiratory resistive loading.

I determined whether prolonged inspiratory resistive loading (IRL) affects phrenic motoneuron discharge, independent of changes in chemical drive. In seven decerebrate spontaneously breathing cats, the discharge patterns of eight phrenic motoneurons from filaments of one phrenic nerve were monitored, along with the global activity of the contralateral phrenic nerve, transdiaphragmatic pressure, and fractional end-tidal CO2 levels. Discharge patterns during hyperoxic CO2 rebreathing and breathing against an IRL (2,500-4,000 cmH2O.1-1.s) were compared. During IRL, transdiaphragmatic pressure increased and then either plateaued or decreased. At the highest fractional end-tidal CO2 common to both runs, instantaneous discharge frequencies in six motoneurons were greater during sustained IRL than during rebreathing, when compared at the same time after the onset of inspiration. These increased discharge frequencies suggest the presence of a load-induced nonchemical drive to phrenic motoneurons from unidentified source(s).

PCO2 affects tracheal tone during apnea in anesthetized dogs.

We hypothesized that CO2, like hypoxia and withdrawal of pulmonary slowly adapting receptor input, would cause tracheal constriction during neural apnea (absence of phrenic activity). In seven anesthetized paralyzed dogs ventilated to neural apnea, we increased arterial PCO2 (PaCO2) in steps by adding CO2 to the inspirate while keeping ventilation constant. Increases in PaCO2 caused tracheal constriction during neural apnea in all dogs; 69 +/- 26 (SD)% of the change in tracheal diameter occurred during neural apnea. Average sensitivity of tracheal diameter to CO2 was 0.44 mm/Torr PaCO2. Our data suggest that central chemoreceptor inputs to brain stem neurons controlling smooth muscle of the extrathoracic airway bypass central mechanisms generating inspiration.

Effects of ethanol on respiratory activity in the neonatal rat brainstem-spinal cord preparation.

Ethanol (1-12 mM) added to the superfusion medium of the isolated brainstem-spinal cords of newborn rats did not affect phrenic activity but significantly reduced hypoglossal activity by 54%, 67% and 55% at 3, 6 and 12 mM, respectively. Although the reasons for the suppression of hypoglossal activity remain unknown, this preparation may be a useful model for determining why cranial motoneurons are more vulnerable than phrenic motoneurons to various agents and, more generally, how ethanol impairs neural function.